Identification of Potential PPAR γ Agonists as Hypoglycemic Agents: Molecular Docking Approach

Mishra, Ganesh Prasad; Sharma, Rajesh

doi:10.1007/s12539-015-0126-7

Cited by 10 publications

(4 citation statements)

References 28 publications

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“…The activity of tyrosinase is the first step in melanogenesis, indicating the oxidation of phenols to ortho -quinones by oxy-tyrosinase [ 47 , 48 ]. The activity mentioned above also shows the oxidation of bisphenol to quinone at the same time [ 2 , 3 , 5 , 13 , 14 , 18 , 32 , 34 , 37 , 38 , 49 ]. Thus, the activity of tyrosinase reflects the whole oxidation process of phenol to quinone through monooxygenase activity.…”

Section: Discussionmentioning

confidence: 99%

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Synergistic Promotion on Tyrosinase Inhibition by Antioxidants

et al. 2018

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When exposed to ultraviolet radiation, the human skin produces profuse reactive oxygen species (ROS), which in turn activate a variety of biological responses. Mounting ROS levels activate tyrosinase by mobilizing α-melanocyte-stimulating hormone in the epidermis and finally stimulates the melanocytes to produce melanin. Meanwhile, the Keap1-Nrf2/ARE pathway, which removes ROS, is activated at increased ROS levels, and antioxidant compounds facilitates the dissociation of Nrf2. In this study, we explored the possible suppressing effects of antioxidant compounds and tyrosine inhibitors on melanin formation and the promotory effects of these compounds on ROS scavenging. The antioxidant activity of glabridin (GLA), resveratrol (RES), oxyresveratrol (OXYR), and phenylethylresorcinol (PR) were investigated via the stable free radical 2,2-diphenyl-1-picrylhydrazyl method. The inhibitory effects of the four compounds and their mixtures on tyrosinase were evaluated. l-Tyrosine or 3-(3,4-dihydroxyphenyl)-l-alanine (l-DOPA) was used as a substrate. The results showed that all mixtures did not exhibit synergistic effects with the l-tyrosine as a substrate, suggesting that l-tyrosine is not suitable as a substrate. However, the mixtures of “GLA:RES,” “GLA:OXYR,” “OXYR:RES,” and “PR:RES” demonstrated synergistic effects (CI < 0.9, p < 0.05), whereas “GLA:RES” and “PR:OXYR” indicated an additive effect (0.9 ditive1, p < 0.05). Furthermore, we used a molecular docking strategy to study the interactions of the four compounds with tyrosinase and l-DOPA. The molecular docking result is consistent with that of the experiment. Finally, we selected RES + OXYR and used PIG1 cells to verify whether OXYR synergistically promotes RES activity on tyrosinase. The two agents had a synergistic inhibitory effect on tyrosinase activity. These results provided a novel synergistic strategy for antioxidants and tyrosinase inhibitors, and this strategy is useful in skin injury treatment.

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Section: Discussionmentioning

confidence: 99%

“…The best docked pose and co-crystallized conformation are then simply aligned, and the RMSD is calculated. A low value indicates accurate docking method [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

Synergistic Promotion on Tyrosinase Inhibition by Antioxidants

et al. 2018

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“…The investigation of the binding power of the aforementioned compounds to the SARS-CoV-2 enzyme protease (6LU7) was conducted through the utilization of molecular docking strategy [ 39 , 40 ]. The generation of the three-dimensional models of the title compounds was done utilizing the builder user interface of MOE [ 41 ].…”

Section: Methodsmentioning

confidence: 99%

An efficient eco-friendly, simple, and green synthesis of some new spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives as potential inhibitors of SARS-CoV-2 proteases: drug-likeness, pharmacophore, molecular docking, and DFT exploration

El-Saghier,

Enaili,

Abdou

et al. 2023

Mol Divers

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Introduction The coronavirus disease 2019 (COVID-19) pandemic has caused a global health crisis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious virus that can cause severe respiratory illness. There is no specific treatment for COVID-19, and the development of new drugs is urgently needed. Problem statement The SARS-CoV-2 main protease (Mpro) enzyme is a critical viral enzyme that plays a vital role in viral replication. The inhibition of Mpro enzyme can be an effective strategy for developing new COVID-19 drugs. Methodology An efficient operationally simple and convenient green synthesis method had been done towards a series of novel spiro-N-(4-sulfamoylphenyl)-2-carboxamide derivatives, in ethanol at room temperature in green conditions, up to 90% yield. The molecular structures of the synthesized compounds were verified using spectroscopic methods.The title compounds were subjected to in silico analysis, including Lipinski’s rule and ADMET prediction, in addition to pharmacophore modeling and molecular docking against the active site of SARS-CoV-2 target main protease (Mpro) enzyme (6LU7). Furthermore, both of the top-ranked compounds (5 and 6) and the standard Nirmatrelvir were subjected to DFT analysis. Findings The synthesized compounds exhibited good binding affinity to SARS-CoV-2 Mpro enzyme, with binding energy scores ranging from − 7.33 kcal/mol (compound 6) and − 7.22kcal/mol (compound 5) to − 6.54 kcal/mol (compounds 8 and 9). The top-ranked compounds (5 and 6) had lower HOMO–LUMO energy difference (ΔE) than the standard drug Nirmatrelvir. This highlights the potential and relevance of charge transfer at the molecular level. Recommendation These findings suggest that the synthesized spiro-N-(4-sulfamoylphenyl)-2-carboxamide derivatives could be potential candidates for COVID-19 drug development. To confirm these drugs' antiviral efficacy in vivo, more research is required. With very little possibility of failure, this proven method could aid in the search for the SARS-CoV-2 pandemic's desperately needed medications. Graphical abstract

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“…Arm I polar residues interact with the carboxylate group: His323 and His449 are involved in salt-bridges interactions, while Ser289 and Tyr473 stabilize the ligand through hydrogen bonds. Arm II residues stabilize the hydrophobic fatty acids tail via van der Waals interactions (Figure 2A) [27,28].…”

Section: Pparγ Ligand Binding Modementioning

confidence: 99%

A Combined Molecular Dynamics and Hydropathic INTeraction (HINT) Approach to Investigate Protein Flexibility: The PPARγ Case Study

Agosta,

Cozzini

2024

Molecules

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Molecular Dynamics (MD) is a computational technique widely used to evaluate a molecular system’s thermodynamic properties and conformational behavior over time. In particular, the energy analysis of a protein conformation ensemble produced though MD simulations plays a crucial role in explaining the relationship between protein dynamics and its mechanism of action. In this research work, the HINT (Hydropathic INTeractions) LogP-based scoring function was first used to handle MD trajectories and investigate the molecular basis behind the intricate PPARγ mechanism of activation. The Peroxisome Proliferator-Activated Receptor γ (PPARγ) is an emblematic example of a highly flexible protein due to the extended ω-loop delimiting the active site, and it is responsible for the receptor’s ability to bind chemically different compounds. In this work, we focused on the PPARγ complex with Rosiglitazone, a common anti-diabetic compound and analyzed the molecular basis of the flexible ω-loop stabilization effect produced by the Oleic Acid co-binding. The HINT-based analysis of the produced MD trajectories allowed us to account for all of the energetic contributions involved in interconverting between conformational states and describe the intramolecular interactions between the flexible ω-loop and the helix H3 triggered by the allosteric binding mechanism.

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Identification of Potential PPAR γ Agonists as Hypoglycemic Agents: Molecular Docking Approach

Cited by 10 publications

References 28 publications

Synergistic Promotion on Tyrosinase Inhibition by Antioxidants

Synergistic Promotion on Tyrosinase Inhibition by Antioxidants

An efficient eco-friendly, simple, and green synthesis of some new spiro-N-(4-sulfamoyl-phenyl)-1,3,4-thiadiazole-2-carboxamide derivatives as potential inhibitors of SARS-CoV-2 proteases: drug-likeness, pharmacophore, molecular docking, and DFT exploration

A Combined Molecular Dynamics and Hydropathic INTeraction (HINT) Approach to Investigate Protein Flexibility: The PPARγ Case Study

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